DYNAMIC THERAPY (PDT)
operation of photo dynamic therapy is simple in theory. The patient is given a
substance (the photo sensitizer) that is absorbed by cells and makes the cells
sensitive to damage by light. PDT has been used for many years to treat skin cancer
and other tumours that are near enough to the surface of the skin to be affected
by light. The question is whether a tumour in the prostate gland can be treated
effectively by this means.
There are two primary points to be considered:
How can light be introduced into the prostate gland?
2. How can PDT be used
to treat systemic disease, since there is a widespread view that prostate cancer
may be systemic by the time it is capable of diagnosis?
In a discussion
in 2008 on the PPML
MAILING LIST, Dr Luis Garcia-Bunuel had this to say regarding the
first of these items:
"In well confined, non-superficial lesions,
PDT would be administered using same approach as with brachytherapy. For the prostate,
it could be called interstitial PDT. As the light has relatively low penetration,
multiple light-emitting probes would have to be placed within the prostate itself
to cover the entire gland. The good side of PDT is that it is a non-ionizing radiation
--and therefore non-carcinogenic-- and it can be repeated as frequently as necessary
with less damage to surrounding tissues than with other methods. It will probably
become an additional weapon, particularly for salvage therapy and for lesions
confined to the prostate.
Although the results of this PHASE
1 TRIAL are not very encouraging, the two most important conclusions
to be derived from it, IMO, are that the preferred wavelength is in the near infrared
and that the light delivery is through optical fibres inserted using a transperineal
brachytherapy template in the same manner as for pellet-delivering probes for
traditional brachytherapy. The infrared wave length is convenient because it still
is in the photosensitizer range and with much better penetration of tissues than
its close neighbour in the red visible range. Although these techniques will probably
undergo refinements, they are likely to be the preferred ones in future trials.
It also appears likely from this trial that interstitial PDT can become a good
additional weapon, but not particularly superior to some of the existing ones,
and only for site-confined deep-seated lesions. For more superficial lesions,
both cutaneous and intraluminal, PDT has already been proved of help, but it is
very unlikely that it will ever be of value in metastatic spreads, as claimed
by some people..
…….[there would be a] necessity for a substantial number
of light-emitting probes to reach all prostate areas. If too few, the effective
distribution will be uneven, with some areas receiving insufficient doses. …….
Even if infrared penetration is much greater than in the red visible range, the
number of probes still has to be sufficient to cover the entire prostate adequately.
I don't get a good idea from my readings of how many probes that would be, and
the answer may await further clinical trials."
As to the treatment
of a systemic or metastasised disease, Dr Luis Garcia-Bunuel had this to say about
claims that using light in the red and infrared range, PDT could reach deep-seated
metastases by surrounding the entire patient with light-emitting diodes (LEDs)
to the tune of 48 thousand of them (!!).
"At the longer wavelengths
of red and infrared, they claim the light can penetrate twelve inches into the
body. That's where scientific facts end and fantasy begins. The reason why non-interstitial
PDT has been mostly used in skin and other superficial lesions is that even at
the longer wavelengths, the penetration of soft tissues is relatively shallow.
From short to long wavelengths, we have the following spectrum:
waves--> ultraviolet --> [visible spectrum (violet through red)]--> near infrared-->
far infrared-->microwaves--> radio. The longer the wavelength, the deeper the
[The suggested] methodology appears to rely on red and near
infrared. It is doubtful that those wavelengths would penetrate deeper than one
or two centimetres Even microwaves don't go as deep as the twelve inches claimed
….That's why one can roast small game birds in a microwave oven, but would have
trouble roasting a regular chicken.
The medical spectrum could be defined
as: Facts--> Sound but unproven theories--> Unsound theories--> Quack claims.
It looks like the theories of advocates of SPDT are moving from the factual end
of the spectrum towards the other end."
So, theoretically, PDT looks
as if it might be a good option for the treatment of prostate cancer where the
disease is confined to the gland, although clearly it will be some time before
studies are concluded and approval gained from the authorities.
that must be considered for any prostate cancer treatment is the question of side
effects or collateral damage. To quote Dr Luis Garcia-Bunuel again:
for potential collateral damage, that ought to be a concern, as is with cryotherapy
and other procedures. It is a misconception to think that only cancer cells collect
the photosensitizer. They do to a greater degree than more mature and less vascularized
tissues, but the normal tissues also absorb the photosynthesizer and still are
As Luis says, part of the issue here is the selectivity
of the photosensitizer and another is how long it remains in the body. Normally
patients using PDT have to be very careful to avoid light, especially sunlight.
Skin exposed to light will get a reaction and will be damaged severely by the
sun , or have rashes and blisters.
In theory, the newer substances being
used in trials are designed to home in on cancer cells (and certain other kinds)
in preference to normal tissue, but this selectivity is not absolute. The possibility
of selectivity being enhanced by chemically combining the photosensitizer with
certain antibodies is being actively pursued. In this way the selectivity of the
photosensitizer is combined with the localized introduction of light to improve
the attacking of just the cells that it is intended to attack. If this is achieved
it would greatly reduce the potential for damaging the cells in the erectile nerves
and the bladder.
Newer applications are also being developed that have
a very short 'life' in the patients' bodies. The aim is to have the photosynthesizer
out of the patients' bodies by the time they leave the recovery room and thus
minimise potential damage.
# 1: After
this piece was written, there was an excellent article published in Nature Clinical
Practice Urology in early 2009 - PHOTODYNAMIC
THERAPY FOR PROSTATE CANCER-A REVIEW OF CURRENT STATUS AND FUTURE PROMISE.
It is a fairly technical article but this paragraph, extracted from the article,
sums up the conclusions of the piece:
benefits of prostate cancer treatment depend upon eradication of cancer within
the gland, while the harms of treatment are related to unwanted effects outside
the gland. When treatment is limited to either the prostate gland itself, or the
areas of cancer within the gland where possible, then there is the potential to
achieve the survival benefits of radical treatments in those men who require it,
while avoiding the associated adverse effects. Such an approach would have to
eradicate clinically relevant cancer, while at the same time leave the structures
that surround the prostate (including the rhabdosphincter, rectum, neurovascular
bundles and ejaculatory apparatus) intact. Eventually, a systemic but targeted
therapy will likely meet these requirements; however, as no obvious compound with
these attributes is currently in clinical studies, it is fair to assume that we
are at least a decade away from such a treatment becoming a reality.
Pathol Toxicol Oncol. 2006;25(1-2):373-87.
Updated results of a phase I
trial of motexafin lutetium-mediated interstitial photodynamic therapy in patients
with locally recurrent prostate cancer.
Verigos K, Stripp DC, Mick R, Zhu
TC, Whittington R, Smith D, Dimofte A, Finlay J, Busch TM, Tochner ZA, Malkowicz
S, Glatstein E, Hahn SM.
Department of Radiation Oncology, University of
Pennsylvania, 3400 Spruce Street, 2 Donner, Philadelphia, PA 19104, USA.
recurrent prostate cancer after treatment with radiation therapy is a clinical
problem with few acceptable treatments. One potential treatment, photodynamic
therapy (PDT), is a modality that uses laser light, drug photosensitizer, and
oxygen to kill tumor cells through direct cellular cytotoxicity and/or through
destruction of tumor vasculature. A Phase I trial of interstitial PDT with the
photosensitizer Motexafin lutetium was initiated in men with locally recurrent
prostate cancer. In this ongoing trial, the primary objective is to determine
the maximally tolerated dose of Motexafin lutetium-mediated PDT. Other objectives
include evaluation of Motexafin lutetium uptake from prostate tissue using a spectrofluorometric
assay and evaluation of optical properties in the human prostate. Fifteen men
with biopsy-proven locally recurrent prostate cancer and no evidence of distant
metastatic disease have been enrolled and 14 have been treated.
were developed using transrectal ultrasound images. The PDT dose was escalated
by increasing the Motexafin lutetium dose, increasing the
732 ran light dose,
and decreasing the drug-light interval. Motexafin lutetium doses ranged from 0.5
to 2 mg/kg administered IV 24, 6, or 3 hr prior to 732 ran light delivery. The
light dose, measured in real time with in situ spherical detectors was 25-100
J/cm2. Light was delivered via optical fibers inserted through a transperineal
brachytherapy template in the operating room. Optical property measurements were
made before and after light therapy. Prostate biopsies were obtained before and
after light delivery for spectrofluorometric measurements of photosensitizer uptake.
patients have completed protocol treatment on eight dose levels without dose-limiting
toxicity. Grade I genitourinary symptoms that are PDT related have been observed.
One patient had Grade II urinary urgency that was urinary catheter related. No
rectal or other gastrointestinal PDT-related tox-icities have been observed to
date. Measurements of Motexafin lutetium demonstrated the presence of photosensitizer
in prostate tissue from all patients. Optical property measurements demonstrated
substantial heterogeneity in the optical properties of the human prostate gland
which supports the use of individualized treatment planning for prostate PDT.
a.. Clinical Trial, Phase I